SynBio, Gene Editing and Other New Stuff: Same Concerns, Supersized.

New words like “synthetic biology”, “GMOs 2.0”, “CRISPR”, and “new biology” are being heard. And new compounds are in our fragrances, flavourings, cosmetics and foods.

The new words are for new techniques of genetic engineering. What are the techniques and their products, and should we be concerned?

New Techniques­

The old techniques of genetic engineering (GMOs 1.0) dealt with organisms, and inserted genes by either blasting them into an organism or transferring them via a virus. This was not very precise.

1. Gene Editing. A new technique is called “gene editing”. It is more on target. It can cut the genetic code of organisms with greater precision, insert new code, remove a code and swap out genes with others. Tools used in gene editing include “CRISPR-Cas9”, “Zinc Finger Nucleus” and “TALEN”.

2. Synthetic Biology. Another new technique is the creation of genetic code from scratch, without involving living organisms. This is called “synthetic biology” or “put together life”. It uses computer design technology to engineer and produce new codes in the lab.

Applications and Technologies

These techniques, when applied, have resulted in far-reaching technologies.

a) Applications of Gene Editing

Gene Drives. A much talked-about technology is “gene drives”. It drives the particular gene down to the offspring and doesn’t allow space for an alternate to arise, as would occur in natural evolution. Once a trait is forced down at the expense of the alternatives, the extinction of the “alternate” offspring is the ultimate result.

Gene drives have so far been used on yeast, fruit flies and 2 mosquito species, but have not yet been released to ecosystems. There is widespread discussion about using them to eradicate mice on islands, mosquitoes, and pests.

GMOs 2.0. Gene editing is also used in agriculture, the old domain of GMOs 1.0. With GMOs 2.0, food is being engineered to insert, delete or replace DNA, and entirely new sequences are being created. Gene edited mushrooms (deletions in a gene for non-browning) and canola oil (a gene removed to tolerate herbicide) have both been commercialized. Monsanto in September, 2016 licensed the use of CRISPR to engineer food and Dupont in October 2015 predicted that CRISPR plants would be on dinner plates within 5 years. Proponents of gene editing argue that the resulting organisms are not “GM” or “novel substances”, and therefore aren’t subject to current regulation.

b) Applications of SynBio

Foods, Flavours, Fragrances. The synbio technique has spawned many new applications, including the creation of new compounds in consumer products that are so similar to existing products consumers can’t tell the difference. The method used is to engineer artificial code into microbes and then ferment them on a large scale in vats. Manufacturers use the word “natural” because fermentation is involved.

New Life Forms. Another application is the engineering of completely new genetic codes and life forms. Current players in this sphere include the “DIY” community, students, and start-ups. A code can be created on the computer and 3-D printed. The International Genetically Engineered Machine Competition (IGEM) is a university and high school competition for building “biobricks” (like lego) to operate in living cells. A recent commercial example of a new life form is a plant that glows in the dark.

Bio Weapons. A third application is military. In the US, the Defense Advanced Research Projects Agency (DARPA) provides the most funding for synthetic biology in the US government (although the extent to which this is funnelled to bioweapons is not known). In the US, the Army, Navy and Office of the Secretary of State are also funding synbio. (See Extreme Genetic Engineering and the Human Future, p 31).

What is the Concern?

The concern is we don’t know if the new technologies are safe. Why not? Because we don’t completely understand the interactions that occur in living organisms and ecological systems.

Organisms are complex systems in which chemical reactions “fire” at different times and places along interconnected pathways. They do not behave in linear “cause and equal effect” ways, in either space or time. A gene is part of this system. It is a strand of DNA that messages or “fires” at times (or refrains from “firing”) and brings about an action or change in an organism. Similarly, ecological systems are complex systems. They rely on species interconnections and interactions which also don’t behave in linear “cause and equal effect” ways.

If a complex system does not behave in a linear fashion, the workings of the systems cannot be known ahead of time and its effects cannot be predicted. Similarly, the effects resulting from a change to one aspect of a system cannot be predicted. The effects can only be known “after the fact”, and, depending on the system, these effects may vary.

This inability to predict the results of a change in the system was the problem with GMOs 1.0, and is the same problem with these new techniques. The concern will exist every time one of the new techniques is used in a complex living system. The scientific literature even acknowledges that there are often “unintended” or “unpredicted effects” associated with the products of genetic manipulation. New substances are often created. Even CRISPR-Cas9 technology admittedly has the problem of being “off-target”.

Historical Examples

The concern of unpredictability is underlined by historical examples of GMOs 1.0 gone wrong. In the late 1990s and early 2000s several people died as a result of reactions to gene therapy procedures, the most notable of which was 18 year old Jesse Gelsinger. He died from a severe immune reaction to the viral vector used to transport engineered genes. Another example is the food supplement L-Tryptophan. Genetic modification of the supplement created a new toxin that is linked to EMS, a disease that killed 80 people and afflicted thousands in the late 1980s, early 1990s. (See “L-Tryptophan”).

Examples of agriculture GMOs 1.0 gone wrong include the case of canola. In 1995 Canada became the first country to approve commercialization of genetically engineered canola. GM canola has now spread and eliminated natural canola almost everywhere in Canada. Other examples of GM plants that have spread uncontrollably are: creeping bentgrass in the USA; cotton and maize in Mexico; BT poplar in China; Bt rice in China; and canola in Japan, the US, Australia and the EU. (See Transgene Escape by TestBiotech).

Supersized Concerns

The concern of unpredictability is more pronounced with these new synbio and gene editing techniques than with GMOs 1.0. Reason? The applications of these new techniques are very broad in scope, and their effects can be devastating.

Gene Drives. The scope of gene drives is obviously major. It extends to the possible extinction of a species, and resulting degradation of its ecosystem. Even the National Academy of Sciences of the US, in a June 2016 report (at 86), admits that: “[R]eleasing a gene-drive modified organism into the environment means that a complex molecular system will be introduced into complex ecological systems, potentially setting off a cascade of population dynamics and evolutionary processes that could have numerous reverberating effects”.

GMOs 2.0. The scope of GMOs 2.0 extends to the food humans and animals eat and to the environment. The lack of current regulation and the speed at which the products are being advanced means the GMO 2.0 technologies and products will likely be used before they are assessed. This is even though the effects with GMOs 2.0 are compounded. Testbiotech indicates that with the new gene editing techniques, a single step can be applied several times, causing large changes; plants and animals with genetic changes can be crossed with each other; different techniques can be used in combination with each other; and that even small steps, if repeated, enable radical changes in the genome.

Foods, Flavours, Fragrances. The scope of the synbio application is enormous, on many fronts. The flavours and fragrance market is advancing quickly: it was a US $26.5 billion market in 2016 and is expected to grow to over US $35 billion by 2019. Lux Research indicates synbio will be a “permanent and growing aspect” of the flavours market. A major socioeconomic effect is the displacement of natural botanical farmers: 95% of varieties of natural crops are grown by small-scale farmers, more than 20 million of whom depend on these crops for their livelihood.

The new compounds themselves are pervasive in our consumer products without being identified (except they might be called “natural”). Common names include: method, Ecover, patchouli, PeterThomasRoth, Evolva, Clearwood, TerraVia, Neossance Biossance, Eversweet (in Coca Cola Life), Agarwood Oil, Muufri animal free milk, among others. The effect of these compounds on human beings has not been subject to regulatory assessment, even though they are biologically different than the natural botanical substances.

New Life Forms. The synbio creation of new life forms in the DIY community is advancing, and there is no way to monitor the proliferation of this technology. The September 2016 report of Genome editing: an ethical review points out that a number of websites provide lab and other support services for amateurs, and DIY CRISPR kits are available on line. A code can be 3-D printed and Fedexed for less than $100. The seeds and kit for the new glowing plant can be ordered on-line. The potential for intentional and unintentional release obviously exists, again with no regulations in place.

BioWeapons. The scope of the military application of synbio is not known, but appears to be growing as increasing amounts of government funding are directed toward the technology. The obvious risks are the inability to recall a release, and the potential for a release to be off-target.

In Sum

New technologies are advancing quickly and new products and substances are in our world. Genes can now be created from scratch, a wide array of new products and foods can be created with greater precision, and whole species can be affected. The concerns around safety and unpredictability are the same, but the resulting risk profile has increased dramatically. We would do well to learn the new words.